Intradialytic hypotension (IDH) is associated with increased morbidity and mortality and causes delays in patient care during and immediately after dialysis. It remains one of the most vexing problems associated with dialysis therapy, occurring in approximately 25% of all dialysis treatments, affecting 75,000 patients and twelve million hemodialysis sessions per year. IDH often causes abdominal pain, nausea, vomiting, muscle cramps, dizziness and fainting, slows or terminates the dialysis run, reduces the quality of dialysis, and costs significant amount of nursing time and associated resources. Current therapies to prevent or treat symptomatic hypotension include: decreasing the ultrafiltration rate, reducing the amount of fluid removed during the treatment, treatment with hypertonic saline, administration of fluid boluses or other agents, and placing the patient supine. Most of these countermeasures have a negative impact on the patient and the quality of the dialysis. In this proposal we will evaluate whether an impedance threshold device (ITD), a novel technology invented by the sponsor to enhance negative intrathoracic pressure and augment cardiac preload, can effectively treat and prevent hypotension during dialysis. The ITD works by providing a small amount of airway resistance during spontaneous inspiration, thereby creating an intrathoracic vacuum that draws venous blood back to the heart each time the patient takes a breath. This results in improved cardiac output and an increase in systolic and diastolic blood pressures. The specific aims of this research include 1) demonstrating proof of concept of the ITD to treat IDH in a randomized, blinded, parallel design clinical trial, and 2) demonstrating proof of concept of the ITD to prevent IDH in a randomized, blinded, crossover design clinical trial. A successful clinical trial result will provide proof of concept for use of this new non-invasive therapy to treat and prevent IDH and provide the foundation for a larger study focused on reducing morbidity and mortality from this challenging and harmful complication of dialysis. [unreadable] [unreadable] [unreadable]